Osteoarthritis action alliance consensus opinion - best practice features of anterior cruciate ligament and lower limb injury prevention programs.
To identify best practice features of an anterior cruciate ligament (ACL) and lower limb injury prevention programs (IPPs) to reduce osteoarthritis (OA). This consensus statement started with us performing a systematic literature search for all relevant articles from 1960 through January 2017 in PubMed, Web of Science and CINAHL. The search strategy combined the Medical Subject Heading (MeSH) and keywords for terms: (1) ACL OR "knee injury" OR "anterior cruciate ligament"; (2) "prevention and control" OR "risk reduction" OR "injury prevention" OR "neuromuscular training"; and (3) meta-analysis OR "systematic review" OR "cohort study" OR randomized. We found 166 different titles. The abstracts were reviewed for pertinent papers. The papers were reviewed by at least two authors and consensus of best practice for IPP to prevent OA was obtained by conference calls and e-mail discussions. All authors participated in the discussion. The best practice features of an IPP have the following six components: (1) lower extremity and core strengthening; (2) plyometrics; (3) continual feedback to athletes regarding proper technique; (4) sufficient dosage; (5) minimal-to-no additional equipment; and (6) balance training to help prevent injuries. Exercises focused on preventing ankle sprains, hamstring injuries and lateral trunk movements are important. Plyometric exercises should focus on correcting knee valgus movement. Exercises should focus on optimizing the hamstring to quadriceps strength ratio. In order for IPP to be successful, there should be increased education and verbal feedback along with increased athletic compliance. Additional equipment is not necessary. Balance training alone does not significantly reduce injuries, but is beneficial with other exercises. Not enough evidence to recommend stretching and agility exercises, with no ill effects identified. Therefore, we suggest making these optional features. Best practice features for ACL and lower limb IPPs to help prevent OA contain six key components along with two optional.


Predictors of injury mortality in early childhood.
To study the association between maternal/infant characteristics and mortality from injury for children 0 through 4 years of age. Historical cohort. State of Tennessee. Children 0 through 4 years of age at any time between January 1, 1985 and December 31, 1994. We linked birth certificates and US census data to obtain information on maternal age, race, education, neighborhood income, parity, use of prenatal care, residence location, infant's gender, and gestational age. The outcome was death from injury, as determined from linked death certificates. The incidence density rates for each stratum (defined by maternal/child characteristics) were calculated by dividing the number of injury deaths by child years in the stratum. We used multivariate analysis to assess the independent contribution of each characteristic to risk of injury death. There were 1 035 504 children 0 through 4 years of age who contributed 3 414 436 child years. There were 803 deaths from injury, ie, 23.5 deaths per 100 000 child years. In the multivariate analysis, children had at least a 50% increased risk of injury mortality if they were born to a mother who had less than a high school education (relative risk [RR] = 2.88; 95% confidence interval [CI]: 1.92-4.34) compared with a college education, was <20 years of age (RR = 2.42; 95% CI: 1.76-3.31) compared with >30 years, or had >2 other children (RR = 2.97; 95% CI: 2.29-3.85) compared with no other children. Neither race nor income was significantly associated with childhood injury mortality in the multivariate analysis. Classification of children by maternal education, age, and parity defined a pronounced risk gradient in which high-risk children had an injury mortality rate >15 times that of low-risk children. The steep risk gradient was present for both infants (24-fold increase for high-risk children) and children 1 through 4 years of age (13-fold increase for high-risk children). If the injury mortality rate for all children were equal to that of the low-risk group, 614/803 (76.3%) of injury deaths would not have occurred. For young children, maternal education, age, and parity are strongly and independently associated with injury mortality. These factors define a steep gradient of risk, suggesting that many injury deaths could be prevented.


[Spatial representation of a two-dimensional pattern].
The purpose of this study was (a) to determine if vision and kinesthesis contribute differentially to the coding of a specific two-dimensional pattern and (b) to identify the effect of repetition on the spatial representation of this pattern. The reproductions of a specific pattern presented visually were compared with those of a pattern presented kinesthetically. The results showed that vision and kinesthesis had contributed equally to the coding of the directional components of the pattern. However, there was dominance of visual information over kinesthetic information when coding the distance between the intersecting points of the pattern, especially at the beginning of the process. Generally speaking, the visual or kinesthetic repetition, or both, have increased favourably the precision with which a specific pattern was reproduced in distance and direction.


[Hyperthermia as cytotoxic and radiosensitizing agent: cellular effects--a review].
Some aspects of the effect of hyperthermia on mammalian cells are presented. Hyperthermia is an efficient means to kill cells or to reinforce the action of radiation. These effects depend on temperature. Between both effects exists a steep temperature gradient, making necessary an exact measurement of temperature. The cytotoxic effect prefers radioresistant cells such as hypoxic cells or cells in the late DNA synthesis phase. A combination will be favorable because both therapy methods supplement each other, but produce no interaction. If one wishes to take advantage of the radiosensitizing effect, hyperthermia intervenes in the processes of recovery after the radiation insult. It is therefore indicated especially in case of tumors presenting a great capacity of cells recovery. Here, a real interaction between hyperthermia and radiotherapy takes place at the same target. Cellular death after hyperthermia and radiotherapy is caused by different mechanisms. All these data suggest the following recommendations for clinical practice: The temperature should be chosen higher or lower than 42 degrees C depending on the desired effect (cytotoxic or radiosensitizing effect). Under the point of view of recovery, radiotherapy should be followed by hyperthermia. In order to avoid an induction of resistance against hyperthermal treatment, hyperthermia should be combined as often as possible with radiotherapy.


Analysis of Physiological Response of Attention and Stress States in Teleoperation Performance of Social Tasks.
Some studies addressed monitoring mental states by physiological responses analysis in robots' teleoperation in traditional applications such as inspection and exploration; however, no study analyzed the physiological response during teleoperated social tasks to the best of our knowledge. We analyzed the physiological response of attention and stress mental states by computing the correlation between multimodal biomarkers and performance, pleasure-arousal scale, and workload. Physiological data were recorded during simulated teleoperated social tasks to induce mental states, such as normal, attention, and stress. The results showed that task performance and workload subscales achieved moderate correlations with some multimodal biomarkers. The correlations depended on the induced state. The cognitive workload was related to brain biomarkers of attention in the frontal and frontal-central regions. These regions were close to the frontopolar region, which is commonly reported in attentional studies. Thus, some multimodal biomarkers of attention and stress mental states could monitor or predict metrics related to the performance in teleoperation of social tasks.


Tumor response assessment to treatment with [177Lu-DOTA0,Tyr3]octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors: differential response of bone versus soft-tissue lesions.
We have noted that bone lesions on CT respond differently from soft-tissue lesions to treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate). We therefore compared the response of bone lesions with that of soft-tissue lesions to treatment with (177)Lu-octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors (NETs). Forty-two patients with well-differentiated NETs who had bone metastases that were positive on [(111)In-DTPA(0)]octreotide somatostatin receptor scintigraphy (SRS) before treatment, and who had soft-tissue lesions, were studied. All patients had had a minimum of 1 follow-up CT scan. Lesions were scored on CT and bone lesions also on SRS before and after treatment. Tumor markers (chromogranin A and 5-hydroxyindoleacetic acid) before and after treatment were compared. Because bone lesions were not visible on CT before treatment in 11 of 42 patients (26%), bone and soft-tissue lesions were evaluated in 31 patients. Whereas bone lesions increased in size, soft-tissue lesions decreased in size. The percentage change in bone and soft-tissue lesions was significantly different at all time points up to 12 mo of follow-up (P < 0.001). The intensity or number of bone lesions on SRS decreased after treatment in 19 of 23 patients (83%) in whom SRS after treatment was available. The tumor markers also decreased significantly after treatment. In 1 patient, bone lesions became visible on CT after treatment, mimicking progressive disease with "new" bone lesions, although there was an overall treatment response. In patients with NETs, the apparent increase in size of bone lesions or the appearance of new bone lesions on CT after treatment with (177)Lu-octreotate should be interpreted cautiously, as this finding may be therapy-related rather than indicative of tumor progression.


An algorithm for Parkinson's disease speech classification based on isolated words analysis.
Automatic assessment of speech impairment is a cutting edge topic in Parkinson's disease (PD). Language disorders are known to occur several years earlier than typical motor symptoms, thus speech analysis may contribute to the early diagnosis of the disease. Moreover, the remote monitoring of dysphonia could allow achieving an effective follow-up of PD clinical condition, possibly performed in the home environment. In this work, we performed a multi-level analysis, progressively combining features extracted from the entire signal, the voiced segments, and the on-set/off-set regions, leading to a total number of 126 features. Furthermore, we compared the performance of early and late feature fusion schemes, aiming to identify the best model configuration and taking advantage of having 25 isolated words pronounced by each subject. We employed data from the PC-GITA database (50 healthy controls and 50 PD patients) for validation and testing. We implemented an optimized k-Nearest Neighbours model for the binary classification of PD patients versus healthy controls. We achieved an accuracy of 99.4% in 10-fold cross-validation and 94.3% in testing on the PC-GITA database (average value of male and female subjects). The promising performance yielded by our model confirms the feasibility of automatic assessment of PD using voice recordings. Moreover, a post-hoc analysis of the most relevant features discloses the option of voice processing using a simple smartphone application.


A population-based study of transdermal fentanyl initiation in Australian clinical practice.
Although guidelines caution against initiation of transdermal (TD) fentanyl among those who are opioid naïve, there is concern that not all people receive adequate prior opioid exposure. This study examined the percentage of people who are opioid naïve at the time of TD fentanyl initiation in Australia; strengths initiated; and characteristics associated with being opioid naïve. This is a national retrospective cohort study derived from a 10% sample of Pharmaceutical Benefits Scheme concessional beneficiaries initiating TD fentanyl between 29 September 2009-31 December 2013. Individuals were deemed opioid naïve if they had no opioid dispensings in the previous 90 days. Logistic regression was used to determine characteristics associated with being opioid naïve, including socio-demographics, likely comorbidities and previous analgesic use. A total of 13,166 people initiated TD fentanyl; 60.4% were female and 76.2% were aged ≥ 65 years. Three in ten (30.4%) were opioid naïve and 63.2% initiated the 12 mcg/h patch. Those who were opioid naïve were more likely to be female (adjusted odds ratio (aOR) 1.35; 95% CI 1.25-1.46), older (aOR 1.85; 95% CI 1.54-2.28 for those ≥ 85 years) and previously dispensed medicines for dementia (aOR 1.37; 95% CI 1.04-1.80). People previously dispensed medicines for cancer were less likely to be opioid naïve (aOR 0.57; 95% CI 0.48-0.67). Three in ten Australians initiating TD fentanyl are opioid naïve. Our findings suggest that specific patient sub-populations already at increased risk of opioid-related adverse events are not receiving prior opioid treatment before initiation, highlighting the need for greater adherence to current treatment guidelines.


Response to methylphenidate in children with attention deficit hyperactivity disorder and manic symptoms in the multimodal treatment study of children with attention deficit hyperactivity disorder titration trial.
Recent reports raise concern that children with attention deficit hyperactivity disorder (ADHD) and some manic symptoms may worsen with stimulant treatment. This study examines the response to methylphenidate in such children. Data from children participating in the 1-month methylphenidate titration trial of the Multimodal Treatment Study of Children with ADHD were reanalyzed by dividing the sample into children with and without some manic symptoms. Two "mania proxies" were constructed using items from the Diagnostic Interview Schedule for Children (DISC) or the Child Behavior Checklist (CBCL). Treatment response and side effects are compared between participants with and without proxies. Thirty-two (11%) and 29 (10%) participants fulfilled criteria for the CBCL mania proxy and DISC mania proxy, respectively. Presence or absence of either proxy did not predict a greater or lesser response or side effects. Findings suggest that children with ADHD and manic symptoms respond robustly to methylphenidate during the first month of treatment and that these children are not more likely to have an adverse response to methylphenidate. Further research is needed to explore how such children will respond during long-term treatment. Clinicians should not a priori avoid stimulants in children with ADHD and some manic symptoms.


Alteration of mitochondrial protein complexes in relation to metabolic regulation under short-term oxidative stress in Arabidopsis seedlings.
Plants reconfigure their metabolic network under stress conditions. Changes of mitochondrial metabolism such as tricarboxylic acid (TCA) cycle and amino acid metabolism are reported in Arabidopsis roots but the exact molecular basis underlying this remains unknown. We here hypothesise the reassembly of enzyme protein complexes to be a molecular mechanism for metabolic regulation and tried in the present study to find out mitochondrial protein complexes which change their composition under oxidative stress by the combinatorial approach of proteomics and metabolomics. Arabidopsis seedlings were treated with menadione to induce oxidative stress. The inhibition of several TCA cycle enzymes and the oxidised NADPH pool indicated the onset of oxidative stress. In blue native/SDS-PAGE analysis of mitochondrial protein complexes the intensities of 18 spots increased and those of 13 spots decreased in menadione treated samples suggesting these proteins associate with, or dissociate from, protein complexes. Some spots were identified as metabolic enzymes related to central carbon metabolism such as malic enzyme, glyceraldehyde-3-phosphate dehydrogenase, monodehydroascorbate reductase and alanine aminotransferase. The change in spot intensity was not directly correlated to the total enzyme activity and mRNA level of the corresponding enzyme but closely related to the metabolite profile, suggesting the metabolism is regulated under oxidative stress at a higher level than translation. These results are somewhat preliminary but suggest the regulation of the TCA cycle, glycolysis, ascorbate and amino acid metabolism by reassembly of plant enzyme complexes.


A qualitative study of DRG coding practice in hospitals under the Thai Universal Coverage scheme.
In the Thai Universal Coverage health insurance scheme, hospital providers are paid for their inpatient care using Diagnosis Related Group-based retrospective payment, for which quality of the diagnosis and procedure codes is crucial. However, there has been limited understandings on which health care professions are involved and how the diagnosis and procedure coding is actually done within hospital settings. The objective of this study is to detail hospital coding structure and process, and to describe the roles of key hospital staff, and other related internal dynamics in Thai hospitals that affect quality of data submitted for inpatient care reimbursement. Research involved qualitative semi-structured interview with 43 participants at 10 hospitals chosen to represent a range of hospital sizes (small/medium/large), location (urban/rural), and type (public/private). Hospital Coding Practice has structural and process components. While the structural component includes human resources, hospital committee, and information technology infrastructure, the process component comprises all activities from patient discharge to submission of the diagnosis and procedure codes. At least eight health care professional disciplines are involved in the coding process which comprises seven major steps, each of which involves different hospital staff: 1) Discharge Summarization, 2) Completeness Checking, 3) Diagnosis and Procedure Coding, 4) Code Checking, 5) Relative Weight Challenging, 6) Coding Report, and 7) Internal Audit. The hospital coding practice can be affected by at least five main factors: 1) Internal Dynamics, 2) Management Context, 3) Financial Dependency, 4) Resource and Capacity, and 5) External Factors. Hospital coding practice comprises both structural and process components, involves many health care professional disciplines, and is greatly varied across hospitals as a result of five main factors.


Contaminated in-house environment contributes to the persistence and transmission of NDM-producing bacteria in a Chinese poultry farm.
While carbapenem use is prohibited in the poultry production chain and carbapenem-resistant Enterobacteriaceae (CRE) are absent from hatchery farms, New Delhi metallo-β-lactamase-producing CRE contamination of commercial broiler chicken farms (grow-out farms) can occur via living hosts such as flies. However, it is not known whether the inanimate factors from in-house environment play a role in the persistence of CRE on commercial farms. Herein, we monitored one typical broiler house in Hebei Province, China, from January 2017 to April 2018. We collected 350 cloacal samples from four broiler batches along with 582 environmental samples (194 in the raising period and 388 in the vacancy period) from sites including the surfaces of drooping boards, feeding troughs, nipple drinkers, corridor floors, sewage trenches, and air. All samples were screened for blaNDM and cultured for NDM-producing isolates. The resistance profiles, genotypes, and genetic context of blaNDM in CRE isolates were further characterized. Results showed that 1-day-old broilers, which were transferred from a hatchery farm and negative for CRE, acquired blaNDM within 24 h of transfer (2 days of age), with a detection rate of up to 18.6%. High blaNDM detection rates (26.8%-31.4%) were obtained among all environmental samples except air after standard cleaning and disinfection during the vacancy period. blaNDM carriage rates (52.9%-72.9%) within the flocks remain stable and high across the next three broiler batches. Overall, 279 NDM-producing bacteria, including 259 Enterobacteriaceae (8 species), 14 Morganellaceae (3 species), three Alcaligenes faecalis and three Pseudomonas putida isolates, were recovered from 85 (24.3%) cloacal and 101 (17.4%) environmental samples. Three NDM variants, including NDM-5 (n = 181), NDM-1 (n = 92), and NDM-9 (n = 3), and a novel NDM-like-metallo-β-lactamase (NLM, n = 3) were identified among the samples. The predominant NDM-producing CRE species among the samples were Klebsiella pneumoniae (CRKP; 32.6%, n = 91) and Escherichia coli (CREC; 27.2%, n = 76). Both clonal and horizontal transmission of blaNDM and an overlap of sequence types (STs) were observed in both CREC and CRKP from chicken and environmental samples. Notably, ST6751 CREC and ST37 CRKP persisted throughout the 16-month surveillance period. IncX3 (n = 197, 7 species), IncA/C2 (n = 41, 5 species), and IncFII (n = 8, E. coli) were the three major blaNDM-carrying plasmid types among the isolates. Although routine cleaning and disinfection procedures and "all-in/all-out" management were performed, once introduced to the farm environment, a diverse range of NDM-positive isolates may survive and persist, becoming an important reservoir of NDM-positive CRE for broiler chickens. Therefore, cleaning and disinfection procedures should be improved on poultry farms to avoid cross-contamination of NDM-producing bacteria between different batches of chickens, as well as further downstream in the poultry production chain.


Using visual design experts in critique-based evaluation of 2D vector visualization methods.
We describe an experiment in which art and illustration experts evaluated six 2D vector visualization methods. We found that these expert critiques mirrored previously recorded experimental results; these findings support that using artists, visual designers and illustrators to critique scientific visualizations can be faster and more productive than quantitative user studies. Our participants successfully evaluated how well the given methods would let users complete a given set of tasks. Our results show a statistically significant correlation with a previous objective study: designers' subjective predictions of user performance by these methods match users measured performance. The experts improved the evaluation by providing insights into the reasons for the effectiveness of each visualization method and suggesting specific improvements.


Reduction of motion artifacts in electrocardiogram monitoring using an optical sensor.
The effectiveness of electrocardiogram (ECG) monitors can be significantly impaired by motion artifacts, which can trigger false alarms, cause misdiagnoses, and lead to inappropriate treatment decisions. Skin stretch associated with patient motion is the most significant source of motion artifacts in current ECG monitoring. In this study, motion artifacts are adaptively filtered by using skin strain as the reference variable, measured noninvasively using an optical sensor incorporated into an ECG electrode. The results demonstrate that this new device and method can significantly reduce motion induced ECG artifacts in continuous ambulatory ECG monitoring.


Clinical aspects of fetal heart auscultation.
The widespread belief that fetal heart tones are first detected with an unamplified fetoscope at about 20 weeks' gestation has been studied prospectively only twice. Using data collection prospectively from 352 visits of 77 patients between 15 and 23 weeks' pregnancy, we studied various clinical aspects of fetal heart tone detection. We determined the gestational age at the time of initial auscultation of fetal heart tones with an ordinary fetoscope, and its relationship to quickening, parity, and placenta location. Fetal heart tones were first identified by auscultation at a mean gestational age of 19.4 weeks (range 17-22 weeks). Detection was possible in 81% of patients examined at 20 weeks and in virtually all patients examined at 21 weeks or later. Once heard, fetal heart tones were identified in every subsequent visit for all patients. Parity and placenta location were significant factors influencing initial fetal heart tone detection. Auscultation preceded quickening in only 12% of patients. Recommendations for using initial fetal heart tone detection in clinical practice are given.


Type distribution of beta-hemolytic streptococci in Israel: a 10-year study.
A survey was carried out over 10 years on the distribution of beta-hemolytic streptococci, their identification, and the clinical implications. Curtures were typed by the conventional agglutination and precipitation methods and by enzyme production. The present survey indicates the changes in streptococcal ecology of the various serotypes. Epidemics of acute pharyngitis with complete absence of rheumatic fever provided suggestive evidence that not all group A types are associated with rheumatic fever. The survey also emphasizes the occurence of non-group A streptococci in human infection.


Aortic pressure-diameter relationship assessed by intravascular ultrasound: experimental validation in dogs.
Intravascular ultrasound (IVUS) has emerged as an important diagnostic method for evaluating vessel diameter and vessel wall motion. To evaluate the validity of IVUS in assessing changes in the pressure-diameter relationship we compared measurements of abdominal aortic diameters derived from IVUS with those simultaneously obtained at the same site using implanted sonomicrometers in five chronically instrumented conscious dogs and in seven acutely instrumented anesthetized dogs. Five hundred eighty beats were analyzed to obtain peak systolic and end-diastolic diameters and to calculate aortic compliance at different blood pressure levels induced either by an aortic pneumatic cuff or by intravenous injections of nitroglycerin or norepinephrine. IVUS agreed closely with sonomicrometer measurements at different blood pressure levels. However, IVUS slightly but significantly underestimated aortic diameters by 0.6 +/- 0.7 mm for systolic diameters (P < 0.001) and by 0.7 +/- 0.6 mm for diastolic diameters (P < 0.001) compared with the sonomicrometer measurements. We conclude that IVUS is a feasible and reliable method to measure dynamic changes in aortic dimensions and has the potential to provide ready access to assess aortic compliance in humans.


Why and how to spare the hippocampus during brain radiotherapy: the developing role of hippocampal avoidance in cranial radiotherapy.
The goal of this review is to summarize the rationale for and feasibility of hippocampal sparing techniques during brain irradiation. Radiotherapy is the most effective non-surgical treatment of brain tumors and with the improvement in overall survival for these patients over the last few decades, there is an effort to minimize potential adverse effects leading to possible worsening in quality of life, especially worsening of neurocognitive function. The hippocampus and associated limbic system have long been known to be important in memory formation and pre-clinical models show loss of hippocampal stem cells with radiation as well as changes in architecture and function of mature neurons. Cognitive outcomes in clinical studies are beginning to provide evidence of cognitive effects associated with hippocampal dose and the cognitive benefits of hippocampal sparing. Numerous feasibility planning studies support the feasibility of using modern radiotherapy systems for hippocampal sparing during brain irradiation. Although results of the ongoing phase II and phase III studies are needed to confirm the benefit of hippocampal sparing brain radiotherapy on neurocognitive function, it is now technically and dosimetrically feasible to create hippocampal sparing treatment plans with appropriate irradiation of target volumes. The purpose of this review is to provide a brief overview of studies that provide a rationale for hippocampal avoidance and provide summary of published feasibility studies in order to help clinicians prepare for clinical usage of these complex and challenging techniques.


The Influence of Post Bleaching Treatments in Stain Absorption and Microhardness.
This study investigated the effects of post bleaching treatments to prevent restaining and the change of enamel surface microhardness after dental bleaching in vitro. Sixty intact human incisor teeth were stained in tea solution and randomly assigned into four groups (n=15). Then samples were bleached for two weeks (8 hours daily) by 15% carbamide peroxide. Tooth color was determined both with a spectrophotometer and visually before bleaching (T1) and immediately after bleaching (T2). Next, it was applied in group 1 fluoride (Naf 2%) gel for 2 minutes, and in group 2 a fractional CO2 laser (10 mJ, 200 Hz, 10 s), and in group 3, nanohydroxyapatite gel for 2 minutes. The bleached teeth in group 4 remained untreated (control group). Then teeth placed in tea solution again. Color examinations were repeated after various post bleaching treatments (T3) and restaining with tea (T4) and color change values recorded. The microhardness was measured at the enamel surface of samples. Data was analyzed using ANOVA, Tukey HSD test and Dunnett T3 (α = 0.05). Directly after bleaching (ΔE T3-T2), the treatment with nanohydroxyapatite showed significantly the least color lapse in colorimetric evaluation. In experimental groups, the color change between T3 and T4 stages (ΔE T4-T3) was significantly lower than control group (P < 0.05). Different methods of enamel treatment caused a significant increase in surface microhardness compared to control group (P < 0.05). Application of fluoride, fractional CO2 laser and nanohydroxyapatite as post bleaching treatments are suggested for prevention of stain absorption and increasing the hardening of bleached enamel.


The effects of berberine on reactive oxygen species production in human neutrophils and in cell-free assays.
The health benefits of berberine have been recognized for years. Even so, its effects on human neutrophils, the first line of immune defense, have not been reported. The purpose of this study was to investigate the effects of berberine on the human neutrophil oxidative burst. Reactive oxygen species production was analyzed by luminol-enhanced chemiluminescence. The analysis was performed in spontaneous and stimulated (phorbol myristate acetate (PMA) or opsonized zymosan particles (OZP)) whole blood and isolated neutrophils in the presence or absence of berberine. The effects of berberine on oxidant production in cell-free assays were evaluated using luminescence (H2O2-peroxidase-luminol) and fluorescence (Oxygen Radical Absorbance Capacity - ORAC) techniques. Berberine decreased the production of reactive oxygen species in human whole blood and isolated neutrophils stimulated with either PMA or OZP with a different efficiency (EC50 was 69 μM and 197 μM for PMA and OZP, respectively). The effect was more pronounced in isolated neutrophils. Cell-free assays showed the antioxidant activity of berberine against peroxyl radicals and hydrogen peroxide. Based on our results, we suggest that the effects of berberine on reactive oxygen species production in human neutrophils are due to its antioxidant activity.


Osteomyelitis of the ribs in the antibiotic era.
A total of 106 cases of rib osteomyelitis were reviewed, including 2 cases described in detail. Mycobacterial and bacterial infections accounted for 47 cases each. Fungal rib osteomyelitis occurred in 11 cases and 1 case was caused by Entamoeba histolytica. Most cases occurred in children and young adults. The mean duration of symptoms before diagnosis was 16, 26 and 32 weeks for bacterial, mycobacterial and fungal rib osteomyelitis, respectively. Common clinical signs were fever (73%), soft tissue mass (64%) and chest pain (60%). Route of infection was defined in 85 cases: 62% from contiguous spread and 38% via haematogenous route of infection. Eighty-nine percent had a favourable outcome after antimicrobial therapy with or without surgery. In conclusion, rib osteomyelitis is a rare infection of various aetiologies. The majority of cases occur in children and young adults and its diagnosis is usually delayed for several weeks.


From visual affordances in monkey parietal cortex to hippocampo-parietal interactions underlying rat navigation.
This paper explores the hypothesis that various subregions (but by no means all) of the posterior parietal cortex are specialized to process visual information to extract a variety of affordances for behaviour. Two biologically based models of regions of the posterior parietal cortex of the monkey are introduced. The model of the lateral intraparietal area (LIP) emphasizes its roles in dynamic remapping of the representation of targets during a double saccade task, and in combining stored, updated input with current visual input. The model of the anterior intraparietal area (AIP) addresses parietal-premotor interactions involved in grasping, and analyses the interaction between the AIP and premotor area F5. The model represents the role of other intraparietal areas working in concert with the inferotemporal cortex as well as with corollary discharge from F5 to provide and augment the affordance information in the AIP, and suggests how various constraints may resolve the action opportunities provided by multiple affordances. Finally, a systems-level model of hippocampo parietal interactions underlying rat navigation is developed, motivated by the monkey data used in developing the above two models as well as by data on neurones in the posterior parietal cortex of the monkey that are sensitive to visual motion. The formal similarity between dynamic remapping (primate saccades) and path integration (rat navigation) is noted, and certain available data on rat posterior parietal cortex in terms of affordances for locomotion are explained. The utility of further modelling, linking the World Graph model of cognitive maps for motivated behaviour with hippocampal-parietal interactions involved in navigation, is also suggested. These models demonstrate that posterior parietal cortex is not only itself a network of interacting subsystems, but functions through cooperative computation with many other brain regions.


Knee menisci segmentation and relaxometry of 3D ultrashort echo time cones MR imaging using attention U-Net with transfer learning.
To develop a deep learning-based method for knee menisci segmentation in 3D ultrashort echo time (UTE) cones MR imaging, and to automatically determine MR relaxation times, namely the T1, T1ρ , and T2∗ parameters, which can be used to assess knee osteoarthritis (OA). Whole knee joint imaging was performed using 3D UTE cones sequences to collect data from 61 human subjects. Regions of interest (ROIs) were outlined by 2 experienced radiologists based on subtracted T1ρ -weighted MR images. Transfer learning was applied to develop 2D attention U-Net convolutional neural networks for the menisci segmentation based on each radiologist's ROIs separately. Dice scores were calculated to assess segmentation performance. Next, the T1, T1ρ , T2∗ relaxations, and ROI areas were determined for the manual and automatic segmentations, then compared. The models developed using ROIs provided by 2 radiologists achieved high Dice scores of 0.860 and 0.833, while the radiologists' manual segmentations achieved a Dice score of 0.820. Linear correlation coefficients for the T1, T1ρ , and T2∗ relaxations calculated using the automatic and manual segmentations ranged between 0.90 and 0.97, and there were no associated differences between the estimated average meniscal relaxation parameters. The deep learning models achieved segmentation performance equivalent to the inter-observer variability of 2 radiologists. The proposed deep learning-based approach can be used to efficiently generate automatic segmentations and determine meniscal relaxations times. The method has the potential to help radiologists with the assessment of meniscal diseases, such as OA.


Effects of altitude on performance of elite track-and-field athletes.
Lower barometric air pressure at altitude can affect competitive performance of athletes in some sports. Reported here are the effects of various altitudes on elite track-and-field athletes' performance. Lifetime track-and-field performances of athletes placed in the top 16 in at least 1 major international competition between 2000 and 2009 were downloaded from the database at tilastopaja.org. There were 132,104 performances of 1889 athletes at 794 venues. Performances were log-transformed and analyzed using a mixed linear model with fixed effects for 6 levels of altitude and random quadratic effects to adjust for athlete age. Men's and women's sprint events (100-400 m) showed marginal improvements of ~0.2% at altitudes of 500-999 m, and above 1500 m all but the 100- and 110-m hurdles showed substantial improvements of 0.3-0.7%. Some middle- and long-distance events (800-10,000 m) showed marginal impairments at altitudes above 150 m, but above 1000 m the impairments increased dramatically to ~2-4% for events >800 m. There was no consistent trend in the effects of altitude on field events up to 1000 m; above 1000 m, hammer throw showed a marginal improvement of ~1% and discus was impaired by 1-2%. Above 1500 m, triple jump and long jump showed marginal improvements of ~1%. In middle-and long-distance runners, altitudes as low as 150 to 299 m can impair performance. Higher altitudes (≥1000 m) are generally required before decreases in discus performance or enhancements in sprinting, triple and long jump, or hammer throw are seen.


Predicting mortality in older adults with kidney disease: a pragmatic prediction model.
To develop mortality risk prediction models for older adults with chronic kidney disease (CKD) that include comorbidities and measures of health status and use not associated with particular comorbid conditions (nondisease-specific measures). Retrospective cohort study. Kaiser Permanente Northwest (KPNW) Health Maintenance Organization. Individuals with severe CKD (estimated glomerular filtration rate<30 mL/min per 1.73 m2; N=4,054; n=1,915 aged 65-79, n=2,139 aged ≥80) who received care at KPNW between 2000 and 2008. Cox proportional hazards analysis was used to examine the association between selected participant characteristics and all-cause mortality and to generate age group-specific risk prediction models. Predicted and observed risks were evaluated according to quintile. Predictors from the Cox models were translated into a points-based system. Internal validation was used to provide best estimates of how these models might perform in an external population. The risk prediction models used 16 characteristics to identify participants with the highest risk of mortality at 2 years for adults aged 65 to 79 and 80 and older. Predicted and observed risks agreed within 5% for each quintile; a 4 to 5 times difference in 2-year predicted mortality risk was observed between the highest and lowest quintiles. The c-statistics for each model (0.68-0.69) indicated effective discrimination without evidence of significant overfit (slope shrinkage 0.06-0.09). Models for each age group performed similarly for mortality prediction at 6 months and 2 years in terms of discrimination and calibration. When validated, these risk prediction models may be helpful in supporting discussions about prognosis and treatment decisions sensitive to prognosis in older adults with CKD in real-world clinical settings.


[Magnetic resonance imaging in the diagnosis of renal neoplasms : MRI - histopathological comparison].
The study evaluates the diagnostic of the MRI in the discovery and characterizing renal neoplasms. The principle of the comparative study of MRI, other diagnostic modalities and histopathological data was applied by the author, using a large pool statistically significant clinical material (419 cases). Renal cell carcinoma--the most wide-spread renal parenchyma's tumor, was selected as a morphological model (302 cases). As a result of this investigation, the MRI semiotics of renal cell carcinoma was more precisely defined and detailed and this method's high level of sensitivity (98.4%) was detected, concerning the detection of such a type of pathology. The MRI data reliably reflect (r > 0.8; P < 0.05) the true morphological structure of the tumor's growth, the secondary tumor's tissue alterations and its interaction with surrounding anatomical formations. Thus, MRI is appreciated as a method of choice for oncological urology.


[Endosonographic findings of benign and malignant lesions in the stomach wall. A prospective comparison with conventional imaging study procedures].
The results of endoscopic ultrasonography in the diagnosis and differentiation of benign and malignant lesions of the stomach was prospectively compared with those obtained by upper endoscopy with biopsy, double-contrast radiography and computed tomography in 15 patients with benign and 26 with malignant gastric lesions. The validity of the methods was established by comparing the results obtained with the long-term course observed clinically in conjunction with an endoscopic-histological follow-up or with the findings on histopathological examination of the operative specimen. Precise diagnosis of the lesion was made by endoscopic ultrasonography in about 90% of cases, a result better than that obtained with radiography or computed tomography. Furthermore, endoscopic ultrasonography had good sensitivity for demonstrating perigastric lymph node enlargement; in this respect it was better than computed tomography, but was not able to distinguish whether the enlargement was benign or malignant: this will only become possible with technical improvement of the instruments.


Improving the reliability of molecular sexing of birds using a W-specific marker.
Molecular techniques for identifying sex of birds utilize length differences between CHD-Z and CHD-W introns, but in some cases these methods can lead to sexing errors. Here we show that an additional W-specific primer can be used in conjunction with a pre-existing sexing primer pair to dramatically improve the reliability of molecular sexing methods. We illustrate the approach with American coots (Fulica americana), a species with CHD-Z polymorphism that could not be accurately sexed using traditional methods. We developed a reverse primer GWR2 designed to sit within the intron of the W chromosome and amplify a distinctively small DNA fragment that serves as a W-specific marker. Analysis of known-sex individuals indicates that this W-specific primer provides an efficient and reliable protocol to identify the sex of F. americana. The development of such sex-specific primers will likely increase the reliability of molecular sexing methods in other birds as well. Comparisons between CHD-Z alleles of coots and common moorhens (Gallinula chloropus) revealed that CHD-Z polymorphism evolved separately in these two closely related species. We discuss the implications of repeated evolution of CHD-Z polymorphisms among birds.


Is there a relationship between right-ventricular and right atrial mechanics and functional capacity in hypertensive patients?
We sought to assess right-ventricular and right atrial deformation in patients with arterial hypertension by two-dimensional speckle tracking imaging and three-dimensional echocardiography (3DE), and define the relationship between right-ventricular mechanics and exercise capacity in the study population. This cross-sectional study included recently diagnosed untreated hypertensive patients, well controlled hypertensive patients, treated patients with unsatisfactory controlled blood pressure and control individuals adjusted by sex and age. All the patients underwent complete two-dimensional echocardiography and 3DE examination, as well as cardiopulmonary exercise testing. Right-ventricular strain, and systolic and early diastolic strain rates were significantly decreased in the untreated and the uncontrolled hypertensive patients in comparison with the controls and the well controlled participants. Similar results were obtained for right atrial strain and strain rates. 3DE right-ventricular volumes were increased, whereas 3DE right-ventricular ejection fraction was decreased in the uncontrolled hypertensive patients in comparison with the controls and the well treated patients. Differences in 3DE right-ventricular volumes disappeared after adjustment for body surface area. Considering the whole study population, global right-ventricular strain (β = 0.29, P = 0.018) and 3D right-ventricular stroke volume (β = 0.22, P = 0.041) were independently associated with peak oxygen uptake (VO(2max)) which was significantly decreased in the untreated and the uncontrolled hypertensive patients in comparison with the remaining two groups. Our study showed that right-ventricular and right atrial mechanics, as well as exercise capacity, are significantly deteriorated in the hypertensive patients who are untreated or ineffectively treated. Global right-ventricular strain and 3DE right-ventricular stroke volume are independently associated with functional capacity in the whole study population.


Development of a Dashboard for Rare Diseases - A Technical Case Report.
About 30 million people suffer from a rare disease in Europe. Those affected face a variety of problems. These include the lack of information and difficult access to scientific knowledge for physicians. For a higher visibility of rare diseases and high-quality research, effective documentation and use of data are essential. The aim of this work is to optimize the processing, use and accessibility of data on rare diseases and thus increase the added value from existing information. While dashboards are already being used to visualize clinical data, it is unclear what requirements are prevalent for rare diseases and how these can be implemented with available development tools so that a highly accepted dashboard can be designed. For this purpose, based on an analysis of the current situation and a requirements analysis, a prototype dashboard for the visualization of up-to-date key figures on rare diseases was developed at the University Hospital Carl Gustav Carus in Dresden. The development was based on the user-centered design process in order to achieve a high-level user-friendliness. The requirements analysis identified parameters that stakeholders wanted to see, focusing primarily on statistical analyses. The dashboard handles the automated calculation of statistics as well as their preparation and provision. The evaluations showed the prototypical dashboard would be considered valuable and used by potential users. This work demonstrates that stakeholders are interested in access to prepared information and exemplifies a way to implement it. The dashboard can increase the usage of existing information in terms of a higher accessibility and thus improve the knowledge about rare diseases.


Prevalence of anal incontinence in 409 patients investigated for stress urinary incontinence.
A clinical questionnaire concerning anorectal symptoms and urodynamic tests was used to investigate 409 women consulting for stress urinary incontinence. To compare urodynamic data, patients were divided into three groups of women who had either stress urinary incontinence associated with incontinence for formed and/or liquid stools or with gas incontinence, or isolated stress urinary incontinence. To take in account the patients'age for data interpretation, a Mantel-Haenszel test or covariate analysis was performed. Anal incontinence was reported in 114 (28%) of the 409 women investigated. The prevalence of incontinence for gas only, for liquid, or for solid stools was 18.3, 9.3, and 1%, respectively. The duration of gas incontinence was longer than that of fecal incontinence or stress urinary incontinence. Difficult defecation was more frequently observed in patients with double incontinence than in patients with only stress urinary incontinence, and the difference was significant between patients with gas incontinence and patients with stress urinary incontinence (53% versus 37%, P = 0. 03). There was no difference in the number of bowel movements per week among the three groups of patients. The number of vaginal deliveries was surprisingly lower in patients with fecal incontinence associated with urinary incontinence than in others. There was no urodynamic feature that could distinguish patients with urinary incontinence and patients with double incontinence. This study confirmed the close relationship between anal and stress urinary incontinence. Neurourol. Urodynam. 18:579-590, 1999.


Secondary cytoreductive surgery outcomes of selected patients with paclitaxel/platinum sensitive recurrent epithelial ovarian cancer.
The aim of this study was to evaluate the effect of secondary cytoreductive surgery (SCRS) on survival and to determine prognostic factors that may predict surgical and survival outcome. Between 1999 and 2011, data of 67 patients who had SCRS for epithelial ovarian cancer were evaluated. Factors that had an impact on survival were determined by statistical analysis. Univariate analysis showed that the number of chemotherapy cycles after primary surgery, CA 125 level at SCRS, number of recurrent tumors, recurrence before SCRS, disease dissemination, and number of chemotherapy cycles after SCRS were significantly associated with disease free survival after SCRS. In multivariate analysis, serum CA125 level, tumor dissemination, and number of chemotherapy cycles after SCRS were significantly associated with disease free survival. Moreover, univariate analysis showed that recurrence before SCRS was significantly associated with overall survival. SCRS may be beneficial for first relapsed, localized paclitaxel/platinum sensitive epithelial ovarian tumors and patients with a low serum CA 125 level and those who will receive ≥ 6 chemotherapy cycles after SCRS. This procedure should be considered in selected patient populations.


The aerodynamics of revolving wings I. Model hawkmoth wings.
Recent work on flapping hawkmoth models has demonstrated the importance of a spiral 'leading-edge vortex' created by dynamic stall, and maintained by some aspect of spanwise flow, for creating the lift required during flight. This study uses propeller models to investigate further the forces acting on model hawkmoth wings in 'propeller-like' rotation ('revolution'). Steadily revolving model hawkmoth wings produce high vertical ( approximately lift) and horizontal ( approximately profile drag) force coefficients because of the presence of a leading-edge vortex. Both horizontal and vertical forces, at relevant angles of attack, are dominated by the pressure difference between the upper and lower surfaces; separation at the leading edge prevents 'leading-edge suction'. This allows a simple geometric relationship between vertical and horizontal forces and the geometric angle of attack to be derived for thin, flat wings. Force coefficients are remarkably unaffected by considerable variations in leading-edge detail, twist and camber. Traditional accounts of the adaptive functions of twist and camber are based on conventional attached-flow aerodynamics and are not supported. Attempts to derive conventional profile drag and lift coefficients from 'steady' propeller coefficients are relatively successful for angles of incidence up to 50 degrees and, hence, for the angles normally applicable to insect flight.


Ectopic expression in the giant fiber system of Drosophila reveals distinct roles for roundabout (Robo), Robo2, and Robo3 in dendritic guidance and synaptic connectivity.
The Roundabout (Robo) receptors have been intensively studied for their role in regulating axon guidance in the embryonic nervous system, whereas a role in dendritic guidance has not been explored. In the adult giant fiber system of Drosophila, we have revealed that ectopic Robo expression can regulate the growth and guidance of specific motor neuron dendrites, whereas Robo2 and Robo3 have no effect. We also show that the effect of Robo on dendritic guidance can be suppressed by Commissureless coexpression. Although we confirmed a role for all three Robo receptors in giant fiber axon guidance, the strong axon guidance alterations caused by overexpression of Robo2 or Robo3 have no effect on synaptic connectivity. In contrast, Robo overexpression in the giant fiber seems to directly interfere with synaptic function. We conclude that axon guidance, dendritic guidance, and synaptogenesis are separable processes and that the different Robo family members affect them distinctly.


Survival of Recombinant Monoclonal Antibodies (IgG, IgA and sIgA) Versus Naturally-Occurring Antibodies (IgG and sIgA/IgA) in an Ex Vivo Infant Digestion Model.
To prevent infectious diarrhea in infants, orally-supplemented enteric pathogen-specific recombinant antibodies would need to resist degradation in the gastrointestinal tract. Palivizumab, a recombinant antibody specific to respiratory syncytial virus (RSV), was used as a model to assess the digestion of neutralizing antibodies in infant digestion. The aim was to determine the remaining binding activity of RSV F protein-specific monoclonal and naturally-occurring immunoglobulins (Ig) in different isoforms (IgG, IgA, and sIgA) across an ex vivo model of infant digestion. RSV F protein-specific monoclonal immunoglobulins (IgG, IgA, and sIgA) and milk-derived naturally-occurring Ig (IgG and sIgA/IgA) were exposed to an ex vivo model of digestion using digestive samples from infants (gastric and intestinal samples). The survival of each antibody was tested via an RSV F protein-specific ELISA. Ex vivo gastric and intestinal digestion degraded palivizumab IgG, IgA, and sIgA (p < 0.05). However, the naturally-occurring RSV F protein-specific IgG and sIgA/IgA found in human milk were stable across gastric and intestinal ex vivo digestion. The structural differences between recombinant and naturally-occurring antibodies need to be closely examined to guide future design of recombinant antibodies with increased stability for use in the gastrointestinal tract.


Chronic antiepileptic drug use and functional network efficiency: A functional magnetic resonance imaging study.
To increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug (AED) treatment. The relation between functional magnetic resonance-acquired brain network measures, AED use, and cognitive function was investigated. Three groups of patients with epilepsy with a different risk profile for developing cognitive side effects were included: A "low risk" category (lamotrigine or levetiracetam, n = 16), an "intermediate risk" category (carbamazepine, oxcarbazepine, phenytoin, or valproate, n = 34) and a "high risk" category (topiramate, n = 5). Brain connectivity was assessed using resting state functional magnetic resonance imaging and graph theoretical network analysis. The Computerized Visual Searching Task was used to measure central information processing speed, a common cognitive side effect of AED treatment. Central information processing speed was lower in patients taking AEDs from the intermediate and high risk categories, compared with patients from the low risk category. The effect of risk category on global efficiency was significant (P < 0.05, ANCOVA), with a significantly higher global efficiency for patient from the low category compared with the high risk category (P < 0.05, post-hoc test). Risk category had no significant effect on the clustering coefficient (ANCOVA, P > 0.2). Also no significant associations between information processing speed and global efficiency or the clustering coefficient (linear regression analysis, P > 0.15) were observed. Only the four patients taking topiramate show aberrant network measures, suggesting that alterations in functional brain network organization may be only subtle and measureable in patients with more severe cognitive side effects.


Redox regulation of sirtuin-1 by S-glutathiolation.
Sirtuin-1 (SIRT1) is an NAD(+)-dependent protein deacetylase that is sensitive to oxidative signals. Our purpose was to determine whether SIRT1 activity is sensitive to the low molecular weight nitrosothiol, S-nitrosoglutathione (GSNO), which can transduce oxidative signals into physiological responses. SIRT1 formed mixed disulfides with GSNO-Sepharose, and mass spectrometry identified several cysteines that are modified by GSNO, including Cys-67 which was S-glutathiolated. GSNO had no effect on basal SIRT1 deacetylase activity, but inhibited stimulation of activity by resveratrol (RSV) with an IC(50) of 69 microM. These observations indicate that S-glutathiolation of SIRT1 by low concentrations of reactive glutathione can modulate its enzymatic activity.


[Analysis of tobacco style features using near-infrared spectroscopy and projection model].
In the present paper, a total of 4,733 flue-cured tobacco samples collected from 2003 to 2012 in 17 provincial origins and 5 ecological areas were tested by near infrared spectroscopy, including the NONG(Luzhou) flavor 1,580 cartons, QING (Fen) flavor 2004 cartons and Intermediate flavor 1 149 cartons. Using projection model based on principal component and Fisher criterion (PPF), Projection analysis models of tobacco ecological regions and style characteristics were established. Reasonableness of style flavor division is illustrated by the model results of tobacco ecological areas. With the Euclidean distance between the predicted sample projection values and the mean projection values of each class in style characteristics model, a description is given for the prediction samples to quantify the extent of the style features, and their first and second close categories. Using the dispersion of projected values in model and the given threshold value, prediction results can be refined into typical NONG, NONG to Intermediate, Intermediate to NONG, typical Intermediate, Intermediate to QING, QING to Intermediate, typical QING, QING to NONG, NONG to QING, or super-model range. The model was validated by 35 tobacco samples obtained from the re-dryingprocess in 2012 with different origins and parts. This kind of analysis methods not only can achieve discriminant analysis, but also can get richer feature attribute information and provide guidance to raw tobacco processing and formulations.


The role of CT in the staging and radiotherapy planning of prostatic tumours.
Fifty patients with proven carcinoma of the prostate have been evaluated with CT. The CT studies were carried out for staging and radiotherapy planning and the findings compared with rectal examination and lymphography. CT provided useful additional information to that obtained by rectal examination in 40% of patients and these findings had important implications for radiotherapy planning. There was good correlation between CT and lymphography in the assessment of pelvic lymph node involvement.


Systematic review with meta-analyses and critical appraisal of clinical prediction rules for pulmonary tuberculosis in hospitals.
To systematically review studies evaluating clinical prediction rules (CPRs) for adult inpatients suspected to have pulmonary tuberculosis. Systematic review with meta-analyses. Hospitals. Patients Inpatients at least 15 years of age admitted to acute care. A search was conducted in 5 indexed electronic databases with no language or year of publication restrictions. We performed a meta-analysis for those CPRs with at least 2 validation studies. Results were reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Of the 461 abstracts selected, 36 articles were fully analyzed and 11 articles were included, yielding 8 CPRs derived in 4 countries. Broad validation studies were identified for 2 CPRs. The most frequent clinical predictors were fever and weight loss. All CPRs included chest imaging signs. Most CPRs were derived in countries with a low prevalence of pulmonary tuberculosis and included homeless, immigrants, and those who reacted to the purified protein derivative test. Both of the CPRs derived in countries with a high prevalence of pulmonary tuberculosis strongly relied on chest radiograph predictors. Accuracy of the different CPRs was high (area under receiver operating characteristic curve, 0.79-0.91). Meta-analysis of 4 validation studies for Wisnivesky's CPR indicates optimistic pooled results: sensitivity, 94.1% (95% CI, 89.7%-96.7%); negative likelihood ratio, 0.22 (95% CI, 0.12-0.40). On the basis of a critical appraisal of the 2 best validated CPRs, the presence of weight loss and/or fever in inpatients warrants obtaining a chest radiograph, regardless of the presence of productive cough. If the chest radiograph is abnormal, the patient should be placed in isolation until more specific test results are available. Validation in different settings is required to maximize external generalization of existing CPRs.


Polynucleotide-mediated immunization therapy of cancer.
The novel observations that intramuscular injection of plasmid DNA preparations could result in myocyte gene expression and induce immune responses to encoded immunogens has generated intense interest in the form of gene therapy. This phenomena can occur with both DNA and RNA reagents, and can be used in immune protection (vaccine) or therapy strategies. Immunization with DNA plasmids has generated protective immunity to a wide variety of pathogens and tumor cells in murine animal models. Immune response has occurred in a broad range of animal species following intramuscular injection of plasmid DNA encoding various immunogens as well as following other routes of administration (intravenous, intradermal, etc). The mechanisms responsible for induction of the immune response are as yet unclear, but responses include antibody production, T-cell proliferation, lymphokine release, generation of cytolytic T cells, and delayed hypersensitivity reactions. Plasmid DNA production and purification methods are relatively easy to standardize, and dual expressing plasmids allow incorporation of immune enhancement molecules or second immunogens. Plasmid DNA encoding nontransforming tumor-associated antigens are in development with a National Institutes of Health-approved protocol for carcinoembryonic antigen in colorectal cancer patients. Transforming tumor-associated antigens (eg, HER2/neu) may be approached with RNA or replicative RNA constructs for immunization. The efficacy of this immune approach will soon be examined in clinical trials in patients with cancer and the acquired immunodeficiency syndrome.


Cytoplasmic sulfurtransferases in the purple sulfur bacterium Allochromatium vinosum: evidence for sulfur transfer from DsrEFH to DsrC.
While the importance of sulfur transfer reactions is well established for a number of biosynthetic pathways, evidence has only started to emerge that sulfurtransferases may also be major players in sulfur-based microbial energy metabolism. Among the first organisms studied in this regard is the phototrophic purple sulfur bacterium Allochromatium vinosum. During the oxidation of reduced sulfur species to sulfate this Gammaproteobacterium accumulates sulfur globules. Low molecular weight organic persulfides have been proposed as carrier molecules transferring sulfur from the periplasmic sulfur globules into the cytoplasm where it is further oxidized via the "Dsr" (dissimilatory sulfite reductase) proteins. We have suggested earlier that the heterohexameric protein DsrEFH is the direct or indirect acceptor for persulfidic sulfur imported into the cytoplasm. This proposal originated from the structural similarity of DsrEFH with the established sulfurtransferase TusBCD from E. coli. As part of a system for tRNA modification TusBCD transfers sulfur to TusE, a homolog of another crucial component of the A. vinosum Dsr system, namely DsrC. Here we show that neither DsrEFH nor DsrC have the ability to mobilize sulfane sulfur directly from low molecular weight thiols like thiosulfate or glutathione persulfide. However, we demonstrate that DsrEFH binds sulfur specifically to the conserved cysteine residue DsrE-Cys78 in vitro. Sulfur atoms bound to cysteines in DsrH and DsrF were not detected. DsrC was exclusively persulfurated at DsrC-Cys111 in the penultimate position of the protein. Most importantly, we show that persulfurated DsrEFH indeed serves as an effective sulfur donor for DsrC in vitro. The active site cysteines Cys78 of DsrE and Cys20 of DsrH furthermore proved to be essential for sulfur oxidation in vivo supporting the notion that DsrEFH and DsrC are part of a sulfur relay system that transfers sulfur from a persulfurated carrier molecule to the dissimilatory sulfite reductase DsrAB.


Assessment of the adherence to and costs of the prophylaxis protocol for venous thromboembolism.
Evaluate adherence to the therapeutic prophylaxis protocol for venous thromboembolism (VTE) as well as the costs of this practice. A descriptive and cross-sectional study was conducted at a State General Hospital in Brazil through reports of drug dispensions, prescriptions and risk stratification of patients. Adherence to the VTE prophylaxis protocol was monitored. The tests for VTE diagnosis measured the adherence to therapeutic prophylaxis treatment, and the purchase prices of the drugs went into the calculation of drug therapy costs. The level of adherence to prescriptions for VTE prophylaxis in the hospital was classified as "adherence", "non-adherence" and "justified non-adherence" when compared with the protocol. Protocol adherence was observed for 50 (30.9%) patients, and non-adherence was observed for 63 (38.9%) patients, generating an additional cost of $180.40/month. Justified non-adherence in 49 (30.2%) patients generated $514.71/month in savings due to a reduction in the number of daily administrations of unfractionated heparin while still providing an effective method for preventing VTE. Twenty-six patients stratified as having medium to high risk of VTE who did not receive prophylaxis were identified, generating $154.41 in savings. However, these data should be evaluated with caution since the risks and outcomes associated with not preventing VTE outweigh the economy achieved from not prescribing a drug when a patient needs it. The only case of VTE identified during the study period was related to justified non-adherence to the protocol. The protocol is based on scientific evidence that describes an effective therapy to prevent VTE. However, the protocol should be updated because the justifications for non-adherence are based on scientific evidence, and this justified non-adherence generates savings and yields effective disease prevention.


Physicochemical evaluation of silica-glass fiber reinforced polymers for prosthodontic applications.
This investigation was designed to formulate silica-glass fiber reinforced polymeric materials. Fused silica-glass fibers were chosen for the study. They were heat-treated at various temperatures (500 degrees C, 800 degrees C and 1100 degrees C), silanized, sized and incorporated in two modified resin mixtures (A and B). The flexural properties in dry and wet conditions were tested and statistically analyzed, and the content of residual methyl methacrylate (MMA) monomer, dimensional changes with temperature, water sorption and solubility were determined. Woven fibers [36.9% (wt/wt)], heat-treated at 500 degrees C, gave the highest strength values for the polymeric composites (an ultimate transverse strength of 200 Mpa and a flexural modulus of 10 GPa) compared with the fibers heat-treated at other temperatures. There was no statistically significant difference in the measured flexural properties between resins A and B regarding fiber treatment and water storage time. These fiber composites had a small quantity of residual MMA content [0.37 +/- 0.007% (wt/wt)] and very low water solubility, indicating good biocompatibility. It was suggested that silica-glass fibers could be used for reinforcement as a result of their anticipated good qualities in aqueous environments, such as the oral environment.


TROY, a newly identified member of the tumor necrosis factor receptor superfamily, exhibits a homology with Edar and is expressed in embryonic skin and hair follicles.
In a signal sequence trap screening of the murine brain, we identified a new member of the tumor necrosis factor receptor superfamily designated TROY. TROY is a type I membrane protein of 416 amino acids with characteristic cysteine-rich motifs in the extracellular domain and a tumor necrosis factor receptor-associated factor (TRAF) 2 binding sequence in the cytoplasmic domain of 223 amino acids. In fact, activation of nuclear factor kappaB was induced by the overexpression of TROY and inhibited by dominant negative forms of TRAF2, TRAF5, and TRAF6, indicating that TRAFs and nuclear factor kappaB are involved in the signal transduction of TROY. We also cloned a cDNA for a human counterpart, which showed a 75% homology with mouse TROY at the amino acid level. The extracellular domain of TROY exhibits an extensive homology with that of Edar, a receptor that specifies hair follicle fate. TROY mRNA is strongly expressed in brain and embryo and moderately expressed in the heart, lung, and liver but not the spleen. In the embryo, the expression level is particularly strong in the skin. Interestingly, in situ hybridization analysis of the embryo showed that TROY mRNA was exclusively expressed in the epithelium of many tissues. On the other hand, in neonatal mice, TROY is expressed in hair follicles like Edar as well as in the cerebrum, suggesting pleiotropic functions of TROY in development as well as in the adult mice. The Troy gene is located near the waved coat (Wc) locus, a mutant related to abnormalities in skin and hair.


DNA-binding abilities of bisguanylhydrazones of anthracene-9,10-dicarboxaldehyde.
DNA-binding strengths of three anthracene-9,10-dicarboxaldehyde hydrazones were examined by spectral shifts of the drug-DNA combinations, spectral titration by Scatchard plots, elevation of DNA melting temperature during complexation and comparison of spectral shifts in the presence of DNA's having variable base contents. Dissociation of the DNA-complexes was also observed. The results showed a strong degree of binding by the three compounds. They did not exhibit noticeable base-pair specificity, but both associated with and dissociated rapidly from DNA. Scatchard plots for DNA association indicated two types of binding; the stronger was most likely due to intercalation of the planar anthracene ring into the DNA double helix. No direct correlation can be drawn between the observed anti-cancer activities and DNA binding affinities of these compounds in vitro.


Evidence for the formation of a covalent thiosulfinate intermediate with peroxiredoxin in the catalytic mechanism of sulfiredoxin.
The typical 2-Cys peroxiredoxins are thiol-peroxidases involved in the physiology of hydrogen peroxide not only as a toxic but also as a signaling molecule. Coordination of these functions depends on the sulfinylation of the catalytic Cys, a modification reversed by ATP-dependent sulfiredoxin, which specifically reduces the sulfinic acid group of overoxidized 2-Cys peroxiredoxins into a sulfenic acid. Sulfiredoxin was originally proposed to operate by covalent catalysis, with formation of a peroxiredoxin-sulfiredoxin intermediate linked by a thiosulfinate bond between the catalytic Cys of both partners, a hypothesis rejected by a study of the human enzyme. To settle the argument, we investigated the catalytic mechanism of Saccharomyces cerevisiae sulfiredoxin, by the characterization of the nature and kinetics of formation of the protein species formed between sulfiredoxin and its substrate in the presence of ATP, using mutants of the non-essential Cys residues of both proteins. We observed the formation of a dithiothreitol-reducible peroxiredoxin-sulfiredoxin species using SDS-PAGE and Western blot analysis, and its mass was shown to correspond to a thiosulfinate complex by high resolution mass spectrometry coupled to liquid chromatography. We next measured indirectly and directly a rate constant of formation of the thiosulfinate species of approximately 2 min(-1), for both wild-type and mutant sulfiredoxins, at least equal to the steady-state rate constant of the reaction, with a stoichiometry of 1:1 relative to peroxiredoxin. Taken altogether, our results strongly argue in favor of the formation of a covalent thiosulfinate peroxiredoxin-sulfiredoxin species as an intermediate on the catalytic pathway.


Bottom-up approach toward single-crystalline VO2-graphene ribbons as cathodes for ultrafast lithium storage.
Although lithium ion batteries have gained commercial success owing to their high energy density, they lack suitable electrodes capable of rapid charging and discharging to enable a high power density critical for broad applications. Here, we demonstrate a simple bottom-up approach toward single crystalline vanadium oxide (VO2) ribbons with graphene layers. The unique structure of VO2-graphene ribbons thus provides the right combination of electrode properties and could enable the design of high-power lithium ion batteries. As a consequence, a high reversible capacity and ultrafast charging and discharging capability is achieved with these ribbons as cathodes for lithium storage. A full charge or discharge is capable in 20 s. More remarkably, the resulting electrodes retain more than 90% of the initial capacity after cycling more than 1000 times at an ultrahigh rate of 190C, providing the best reported rate performance for cathodes in lithium ion batteries to date.


Cardiac 7-transmembrane-spanning domain receptor portfolios: diversify, diversify, diversify.
Enhanced signaling in myocytes by the G protein Gq has been implicated in cardiac hypertrophy and the transition to heart failure. alpha1-Adrenergic receptors (alpha1-ARs) are members of the 7-transmembrane-spanning domain (7-TM) receptor family and signal via interaction with Gq in the heart. The specific effects of a loss of alpha1-AR signaling in the heart are explored by O'Connell et al. in this issue of the JCI (see the related article beginning on page 1005). Paradoxically, gene ablation of the alpha 1A and alpha 1B subtypes in mice results in a maladaptive form of reactive cardiac hypertrophy from pressure overload, with a predisposition to heart failure. Thus signaling to the alpha1-AR (compared with signaling from other receptors such as angiotensin receptors, which also couple to Gq) appears to be specifically required for a normal hypertrophic response. This represents another example of how receptors that share common G proteins have diversified, developing unique signaling programs. These findings may have particular clinical relevance because of the widespread use of alpha1-AR antagonists in the treatment of hypertension and symptomatic prostate enlargement.


The Meningococcal Cysteine Transport System Plays a Crucial Role in Neisseria meningitidis Survival in Human Brain Microvascular Endothelial Cells.
While Neisseria meningitidis typically exists in an asymptomatic nasopharyngeal carriage state, it may cause potentially lethal diseases in humans, such as septicemia or meningitis, by invading deeper sites in the body. Since the nutrient compositions of human cells are not always conducive to meningococci, N. meningitidis needs to exploit nutrients from host environments. In the present study, the utilization of cysteine by the meningococcal cysteine transport system (CTS) was analyzed for the pathogenesis of meningococcal infections. A N. meningitidis strain deficient in one of the three cts genes annotated as encoding cysteine-binding protein (cbp) exhibited approximately 100-fold less internalization into human brain microvascular endothelial cells (HBMEC) than the wild-type strain. This deficiency was restored by complementation with the three cts genes together, and the infectious phenotype of HBMEC internalization correlated with cysteine uptake activity. However, efficient accumulation of ezrin was observed beneath the cbp mutant. The intracellular survival of the cbp mutant in HBMEC was markedly reduced, whereas equivalent reductions of glutathione concentrations and of resistance to reactive oxygens species in the cbp mutant were not found. The cbp mutant grew well in complete medium but not in synthetic medium supplemented with less than 300 μM cysteine. Taking cysteine concentrations in human cells and other body fluids, including blood and cerebrospinal fluid, into consideration, the present results collectively suggest that the meningococcal CTS is crucial for the acquisition of cysteine from human cells and participates in meningococcal nutrient virulence.IMPORTANCENeisseria meningitidis colonizes at a nasopharynx of human as a unique host and has many strains that are auxotrophs for amino acids for their growth. To cause invasive meningococcal diseases (IMD) such as sepsis and meningitis, N. meningitidis passes through epithelial and endothelial barriers and infiltrates into blood and cerebrospinal fluid as well as epithelial and endothelial cells. However, meningococcal nutrients, including cysteine, become less abundant when it more deeply infiltrates the human body even during inflammation, such that N. meningitidis has to acquire nutrients in order to survive/persist, disseminate, and proliferate in humans. This was the first study to examine the relationship between meningococcal cysteine acquisition and the pathogenesis of meningococcal infections. The results of the present study provide insights into the mechanisms by which pathogens with auxotrophs acquire nutrients in hosts and may also contribute to the development of treatments and prevention strategies for IMD.


Distal 10q trisomy associated with bilateral hydronephrosis in infancy.
We present clinical and cytogenetic data on a 2.5 year-old boy with partial monosomy 22p (p11.2-->pter) and distal 10q trisomy (10q24.1-->qter), resulting from maternal t(10;22) reciprocal translocation. The patient had bilateral hydronephrosis and hydroureters but without evidence of vesicoureteral reflux. Our clinical observation suggests that urinary collecting system anomaly may be an integral part of distal 10q trisomy syndrome. We recommend detailed imaging studies of urinary tracts be performed on probands with chromosomal disorders involving a duplication of distal 10q.


Inherited epidermolysis bullosa and squamous cell carcinoma: a systematic review of 117 cases.
Inherited epidermolysis bullosa (EB) comprises a highly heterogeneous group of rare diseases characterized by exacerbated skin and/or mucosal fragility and blister formation after minor mechanical trauma. Level of cleavage in the skin, clinical features with immunofluorescence antigen mapping and/or electron microscopy examination of a skin biopsy and/or gene involved, type(s) of mutation present and sometimes specific mutation(s), allow to define the EB type and subtype. This family of genodermatoses exposes patients to several complications, cutaneous squamous cell carcinoma (cSCC) being the most severe of them. The aim of this systematic review was to document patients with EB who developed cSCC. A systematic literature search was performed, from inception to March 2014, using Medline, Embase, Cochrane and ClinicalTrials.gov databases. Only articles published in English and French were selected. The diagnosis of EB had to be confirmed by EM and/or IFM and/or mutation analysis, while cSCC had to be confirmed by histological analysis. Of 167 references in the original search, 69 relevant articles were identified, representing 117 cases. cSCCs were identified in all types of EB, though predominantly in recessive dystrophic EB (RDEB) forms (81 cases (69.2 %)). The median age at diagnosis was 36 years old (interquartile range (IQR), 27-48 years and range, 6-71 years) for all forms. Of those with measurements in the literature (88 cases (75.2 %)), tumor size was greater than 2 centimeters in 52 cases (59.1 %). The histopathological characteristics were specified in 88 cases (75.2 %) and well-differentiated forms predominated (73.9 %). No conclusion could be drawn on the choice of surgical treatment or the management in advanced forms. This study was retrospective and statistical analysis was not included due to various biases. This study design did not allow to infer prevalence, nor EB subtype risk for cSCC occurrence. Our study correlated with historical data shows that most of the cSCCs occurred in subjects with the RDEB subtype, however reports also show that cSCCs can present in any patients with EB. The first signs of cSCC developed at a younger age in EB patients than in non-EB patients. Interestingly, the cSCC duration, before its diagnosis, was shorter in individuals with RDEB than with junctional EB (JEB) and dominant dystrophic EB (DDEB). This study further emphasizes the importance of regular monitoring of EB patients, particularly with the RDEB subtype as they developed cSCC at a younger age.


Photobiomodulation therapy (PBMT) in bone repair: A systematic review.
Photobiomodulation therapy (PBMT) using low-level laser influences the release of several growth factors involved in the formation of epithelial cells, fibroblasts, collagen and vascular proliferation, besides accelerating the synthesis of bone matrix due to the increased vascularization and lower inflammatory response, with significant increase of osteocytes in the irradiated bone. Considering its properties, beneficial effects and clinical relevance, the aim of this review was to analyze the scientific literature regarding the use of PBMT in the process of bone defect repair. Electronic search was carried out in PubMed/MEDLINEⓇ and Web of Science databases with combination of the descriptors low-level laser therapy AND bone repair, considering the period of publication until the year 2018. The literature search identified 254 references in PubMed/MEDLINE and 204 in Web of Science, of which 33 and 4 were selected, respectively, in accordance with the eligibility requirements. The analysis of researches showed articles using PBMT in several places of experimentation in the subjects, different types of associated biomaterials, stimulatory effects on cell proliferation, besides variations in the parameters of use of laser therapy, mainly in relation to the wavelength and density of energy. Only four articles reported that the laser did not improve the osteogenic properties of a biomaterial. Many studies have shown that PBMT has positive photobiostimulatory effects on bone regeneration, accelerating its process regardless of parameters and the use of biomaterials. However, standardization of its use is still imperfect and should be better studied to allow correct application concerning the utilization protocols.


Robust Sample Preparation of Large-Area In- and Out-of-Plane Cross Sections of Layered Materials with Ultramicrotomy.
Layered materials (LMs) such as graphene or MoS2 have attracted a great deal of interest recently. These materials offer unique functionalities due to their structural anisotropy characterized by weak van der Waals bonds along the out-of-plane axis and covalent bonds in the in-plane direction. A central requirement to access the structural information on complex nanostructures built upon LMs is to control the relative orientation of each sample prior to their inspection, e.g., with transmission electron microscopy (TEM). However, developing sample preparation methods that result in large inspection areas and ensure full control over the sample orientation while avoiding damage during the transfer to the TEM grid is challenging. Here, we demonstrate the feasibility of deploying ultramicrotomy for the preparation of LM samples in TEM analyses. We show how ultramicrotomy leads to the reproducible large-scale production of both in-plane and out-of-plane cross sections, with bulk vertically oriented MoS2 and WS2 nanosheets as a proof of concept. The robustness of the prepared samples is subsequently verified by their characterization by means of both high-resolution TEM and Raman spectroscopy measurements. Our approach is fully general and should find applications for a wide range of materials as well as of techniques beyond TEM, thus paving the way to the systematic large-area mass-production of cross-sectional specimens for structural and compositional studies.


Multiple Myeloma Presenting with Autoimmune Autonomic Ganglionopathy.
Autoimmune autonomic ganglionopathy is an autonomic disorder that occurs as a symptom of paraneoplastic neurological syndrome. To date, there have been no reports on multiple myeloma with autoimmune autonomic ganglionopathy. A 37-year-old Japanese woman suffered from orthostatic hypotension was diagnosed with multiple myeloma (IgG kappa type), and a serological examination revealed the presence of anti-ganglionic nicotinic acetylcholine receptor (anti-gAChR) antibodies. She was treated for multiple myeloma, as a result, the autonomic disturbance improved and her anti-gAChR antibody titer decreased to undetectable levels, despite the fact that she only achieved a partial remission of multiple myeloma. Treatment for multiple myeloma may improve autoimmune autonomic ganglionopathy.


Effect of cyclophosphamide on the solid form of mannitol during lyophilization.
Mannitol is a commonly used bulking agent in lyophilized formulations. It can crystallize into multiple solid forms during lyophilization thereby exhibiting phase heterogeneity and variability in product performance. In this manuscript, we studied the effect of cyclophosphamide (CPA), an anticancer drug, on the solid form of mannitol during lyophilization from aqueous solutions. Freeze-concentration studies were performed in the DSC while lyophilization was performed in a lab scale freeze dryer. DSC experiments revealed two-stage crystallization of mannitol (1.5% w/v) during freeze-concentration, evident as two distinct exothermic events (at -18.2°C and -30°C) in the cooling curve. This was complemented by two eutectic melting endotherms in the subsequent heating curve. Addition of CPA (4.0% w/v) completely inhibited the exotherm at -18.2°C, but enhanced the enthalpy of exotherm at -30°C by five folds. Likewise, only one eutectic melting endotherm was observed in the subsequent heating curve. Lyophilization of the solution containing only mannitol, yielded a mixture of β- (major) and δ- (minor) polymorphs of mannitol. However, in the presence of CPA, only δ-polymorph was observed in the lyophilized sample. This selective favoring of the metastable δ-polymorph over the stable β-polymorph, was explained by altered freezing kinetics of the solution in presence of CPA. The study provides mechanistic insights into solute crystallization behaviour during lyophilization of multi-component systems.


Fibrinogen supplementation after cardiac surgery: insights from the Zero-Plasma trial (ZEPLAST).
Fibrinogen supplementation has been proposed both to prevent and treat postoperative bleeding in cardiac surgery. The optimal fibrinogen concentration trigger and target values and the fibrinogen concentrate dose required remain uncertain. This subanalysis of data from the Zero-Plasma Trial (ZEPLAST) assessed target fibrinogen values and the corresponding fibrinogen concentrate dose for supplementation. We performed a post hoc analysis of 116 subjects included in the randomized, placebo-controlled ZEPLAST trail. Data considered were fibrin-based thromboelastometry (FIBTEM) maximum clot firmness (MCF) determined by whole-blood thromboelastometry (ROTEM) before and after placebo or fibrinogen concentrate, Clauss fibrinogen concentration after placebo or fibrinogen concentrate, postoperative bleeding and severe bleeding (SB). The association between FIBTEM MCF and Clauss fibrinogen concentration was tested with linear regression analyses. The predictive value for SB of FIBTEM MCF and Clauss fibrinogen concentration was tested with receiver operating characteristic analyses. There was a good association between FIBTEM MCF and Clauss fibrinogen concentration in the baseline study population (r(2) = 0.66), which worsened in fibrinogen-supplemented subjects. Both FIBTEM MCF and Clauss fibrinogen concentration yielded a good discriminative power for SB (area under the curve 0.721 and 0.767, respectively). The negative predictive value for SB was 100% for a Clauss fibrinogen concentration of 287 mg dl(-1) and 98% for an FIBTEM MCF of 14 mm. Based on these newly defined target values, the dose of fibrinogen concentrate needed would be 3 g lower than the dose used in ZEPLAST. A dose of fibrinogen concentrate rarely exceeding 2 g might be sufficient to prevent bleeding in cardiac surgery.


Culicoides species community composition and infection status with parasites in an urban environment of east central Texas, USA.
Despite their importance as vectors of zoonotic parasites that can impact human and animal health, Culicoides species distribution across different habitat types is largely unknown. Here we document the community composition of Culicoides found in an urban environment including developed and natural sites in east central Texas, a region of high vector diversity due to subtropical climates, and report their infection status with haemoparasites. A total of 251 individual Culicoides were collected from May to June 2016 representing ten Culicoides species, dominated by C. neopulicaris followed by C. crepuscularis. We deposited 63 sequences to GenBank among which 25 were the first deposition representative for six Culicoides species: C. arboricola (n = 1); C. nanus (n = 4); C. debilipalpis (n = 2); C. haematopotus (n = 14); C. edeni (n = 3); and C. hinmani (n = 1). We also record for the first time the presence of C. edeni in Texas, a species previously known to occur in the Bahamas, Florida and South Carolina. The urban environments with natural area (sites 2 and 4) had higher species richness than sites more densely populated or in a parking lot (sites 1 and 3) although a rarefaction analysis suggested at least two of these sites were not sampled sufficiently to characterize species richness. We detected a single C. crepuscularis positive for Onchocercidae gen. sp. DNA and another individual of the same species positive for Haemoproteus sacharovi DNA, yielding a 2.08% prevalence (n = 251) for both parasites in this species. We extend the knowledge of the Culicoides spp. community in an urban environment of Texas, USA, and contribute to novel sequence data for these species. Additionally, the presence of parasite DNA (Onchocercidae gen. sp. and H. sacharovi) from C. crepuscularis suggests the potential for this species to be a vector of these parasites.


Training and supportive programs for palliative care volunteers in community settings.
Palliative care is specialised health care to support people living with a terminal illness and their families. The involvement of volunteers can extend the range of activities offered by palliative care services, particularly for those living in the community. Activities undertaken by palliative care volunteers vary considerably but can be practical, social or emotional in nature. The types of training and support provided to these volunteers are likely to affect the volunteers' effectiveness in their role and influence the quality of care provided to palliative care clients and their families. Training and support can also have considerable resource implications for palliative care organisations, which makes it important to know how to provide this training and support as effectively as possible. To assess the effects of training and support strategies for palliative care volunteers on palliative care clients and their families, volunteers and service quality. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 28 April 2014); MEDLINE (1946 to 28 April 2014); EMBASE (1988 to 28 April 2014); PsycINFO (1806 to 28 April 2014); CINAHL (EbscoHOST) (1981 to 28 April 2014); ProQuest Dissertations and Theses (1861 to 28 April 2014). We also searched the Database of Abstracts of Reviews of Effects (DARE, The Cochrane Library); reference lists of relevant studies; and conducted an extensive search for evaluations published in government reports and other grey literature including the CareSearch database (www.caresearch.com.au (September 2004 to February 2012) and websites of relevant organisations, for unpublished and ongoing studies. Randomised controlled trials (RCTs), quasi-randomised controlled trials, controlled before-and-after (CBA) studies and interrupted time series (ITS) studies of all formal training and support programs for palliative care volunteers. Programs or strategies in included studies were classified according to any stated or implied purpose: that is, whether they intended to build skills for the volunteer's role, to enhance their coping, or to maintain service standards. Two review authors screened 2614 citations identified through the electronic searches after duplicates were removed. The search of grey literature through websites yielded no additional titles. We identified 28 potentially relevant titles but found no studies eligible for inclusion. We did not find any studies that assessed the effects of training and support strategies for palliative care volunteers that meet our inclusion criteria. The excluded studies suggest that trials in this area are possible. The use of palliative care volunteers is likely to continue, but there is an absence of evidence to show how best to train or support them whilst maintaining standards of care for palliative care patients and their families.


Small-scale convective instability and upper mantle viscosity under california.
Thermal calculations and convection analysis, constrained by seismic tomography results, suggest that a small-scale convective instability developed in the upper 200 kilometers of the mantle under California after the upwelling and cooling of asthenosphere into the slab window associated with the formation of the San Andreas transform boundary. The upper bound for the upper mantle viscosity in the slab window, 5 x 10(19) pascal seconds, is similar to independent estimates for the asthenosphere beneath young oceanic and tectonically active continental regions. These model calculations suggest that many tectonically active continental regions characterized by low upper mantle seismic velocities may be affected by time-dependent small-scale convection that can generate localized areas of uplift and subsidence.


Porcine polymorphonuclear leukocytes generate extracellular microbicidal activity by elastase-mediated activation of secreted proprotegrins.
Antimicrobial peptides of several structural classes have been found in phagocytes and epithelial cells of many animals. The broadly microbicidal protegrins (PG1, -2, and -3) were originally isolated as 16 to 18-amino-acid peptides from pig neutrophil lysates, but the corresponding cDNA sequences encoded much larger precursors that belonged to the cathelicidin family of antimicrobial peptides. We explored the storage, secretion, and microbicidal activation of protegrins in porcine neutrophils and in a model system consisting of recombinant proprotegrin 3 (pPG3) and various serine proteases and their inhibitors. Protegrins were stored in neutrophils as inactive proforms that were cleaved by neutrophil elastase to mature protegrins during the preparation of granule lysate and during phorbol myristate acetate-stimulated granule secretion from intact neutrophils. Recombinant pPG3 was efficiently cleaved by trace amounts of human neutrophil elastase or equivalent amounts of elastase activity from porcine neutrophils, but pPG3 was relatively resistant to porcine pancreatic elastase or human neutrophil cathepsin G. The recombinant pPG3 and neutrophil proprotegrins lacked microbicidal activity, but the mature protegrins generated in the elastase-mediated cleavage reaction were as active against Listeria monocytogenes as the chemically synthesized protegrin. The secretion and elastase-mediated activation of proprotegrins accounted for much of the stable microbicidal activity of porcine neutrophil secretions against L. monocytogenes. Secreted proprotegrins and trace amounts of elastase constitute a binary microbicidal system that is likely to contribute to the antimicrobial activity of porcine inflammatory fluids.


Pain management for children needing laceration repair.
Question An 8-year-old child who lives in a small town has presented to my practice with a 3-inch laceration on the calf that has been assessed and needs repair with sutures. The family lives 4 hours from the nearest emergency department and I was planning to repair the wound in the office. What is the best way to manage pain in young patients needing sutures for laceration repair?Answer Children are particularly susceptible to experiencing high levels of pain and anxiety during routine emergency procedures such as laceration repair. It is important to consider measures to reduce procedural pain. Using needle-free anesthesia, such as the lidocaine-adrenaline-tetracaine combination, might be effective to anesthetize the area. In instances where lidocaine-adrenaline-tetracaine is not sufficient, additional injected lidocaine or bupivacaine can be used. Buffering lidocaine with bicarbonate, warming the lidocaine ampule, and injecting the compound slowly at a perpendicular angle to the skin will reduce pain associated with the injection.